TABLE 6.
Studies describing the predictive value of PBMC GRT in patients with VS switching ART regimens
| Study author and year | No. of patients | Patient characteristics | Sequencing methoda | PBMC GRT results and virologic response |
|---|---|---|---|---|
| Opravil 2002 (173) | 84 | Patients with VS on a PI-containing ART regimen who were switched to a triple NRTI regimen (ABC/3TC/AZT). | Sanger sequencing (PR/RT) | 13 (15%) patients experienced VF. 6/13 had ≥1 ABC-resistance mutation. It was not possible to determine whether these mutations increased the risk of VF. |
| Pellegrin 2003 (172) | 55 | Patients with VS on a PI-containing ART regimen who were switched to a triple NRTI regimen (ABC/3TC/AZT). | Sanger sequencing (PR/RT) | 9/15 (60%) patients with and 8/34 (24%) without ≥1 ABC-resistance mutations experienced VF. The no. of ABC-resistance mutation (P = 0.009) and the PBMC virus load (P = 0.006) were each associated with an increased risk of VF. |
| Porter 2016 (155) | 51 | Patients with VS and no history VF or historical plasma virus resistance to TDF, FTC, or RPV who switched from a PI-containing regimen to TDF/FTC/RPV. Subset of 24 patients with and 27 without K103N history who had stored PBMC samples (SPIRIT trial). | NGS at 10% mutation-detection threshold (PR/RT) | Of 4 patients with VF and emergent HIVDR, 1 had Y181C and M184I detected by PBMC GRT at baseline. E138A (n = 4), E138G (n = 1), E138K (n = 1), and E138Q (n = 1) were present at baseline in patients who did not develop VF. |
| Armenia 2018 (204) | 227 | ART-experienced patients with a history of VS for a median of 4 yrs who underwent PBMC GRT and switched ART. | Sanger sequencing (PR/RT/IN) | 24 mo after switch, 28% of patients with intermediate or full resistance to one of the drugs used at the time of the switch experienced VF compared with 14% lacking genotypic resistance. |
| Ellis 2020 (205) | 83 | Clinic patients undergoing PBMC GRT. 66 switched ART and 59 had postswitch follow-up. 76% had VS and 15% had LLV. 46% had been on ≥2 regimens; 34% lacked a complete ART history. Only 9 had historical plasma virus GRTs. | NGS at 10% mutation-detection threshold (PR/RT/IN) | Among the 24 patients not switching ART, 4 chose not to switch because of the presence of multiclass resistance by PBMC GRT. In a logistic regression model, switching therapy did not appear to increase the risk of subsequent VF. |
| Meybeck 2020 (148) | 185 | Clinic patients undergoing PBMC GRT. 73 switched ART most commonly to an INSTI- (70%) or RPV- (8%) based regimen. The mean no. of previous ART regimens was 5.4. Approx, one-half had historical plasma virus GRTs. | NA | After 6 mo, those who switched therapy had a lower risk of VF than those who continued their original regimen (19% vs. 5%). Other predictors of VF were higher PBMC virus load, lower CD4 nadir, and shorter time of VS. |
| Rodriguez 2021 (206) | 72 | STRUCTR trial participants with VS while on EVG/c/TAF/FTC or EVG/c/TDF/FTC. Patients were switched to ABC/3TC/DTG if PBMC GRT did not detect DRMs associated with this regimen. | NGS at 10% mutation-detection threshold (PR/RT/IN) | 9 of 72 screening patients were found to have resistance to ABC and/or 3TC and therefore did not switch therapy. 50 patients were switched to ABC/3TC/DTG. 44 of 44 evaluable patients maintained VS at wk 48. |
| Overton 2021 (184) | 1045 | Of 1,045 ATLAS-2M participants, 10 had confirmed VF. Patients had been VS for ≥6 mo and had no history of VF or baseline NNRTI or INSTI resistance by plasma virus GRT associated with cabotegravir or RPV, the drugs used for ART simplification. | NGS at 10% mutation-detection threshold (PR/RT/IN) | 5 of 10 patients with confirmed VF had NNRTI resistance by PBMC GRT that was not detected by historical plasma virus GRT, including 3 with major NNRTI-resistance DRMs (Y181C+H221Y; Y188L; Y188L) and 2 with E138A. |
a
Illumina was used for NGS in each study. ABC, abacavir; 3TC, lamivudine; AZT, zidovudine; TDF, tenofovir DF; FTC, emtricitabine; RPV, rilpivirine; EVG/c, elvitegravir/cobicistat; DTG, dolutegravir; NA, details not available or not provided in the study.